**12. Photodynamic therapy in combination with photothermal hyperthermia**

Plasmonic NPs that possess high photothermal conversion, such as those of graphene oxide, are required to enable the combination of PDT and PTT against cancer and other diseases. For example, the conjugation of graphene oxide NPs with folic acid to enable the folate over-expression cancer cell-targeting mechanism and chlorin-e6 to enable PDT was reported to enhance the cancer cell uptake and retention and to selectively kill cancer cells *in vitro* [112]. In this study, MCF-7 cancer cell lines were studied by confocal electron microscopy. These studies revealed that the folic acid and chlorin-e6-functionalized graphene oxide NPs were localized well within the cytoplasm and not on the cell membrane. This supported the folic acidenabled endocytosis of the graphene oxide nanoconjugate.

Gold NPs are well-known for their photoacoustic and photothermal properties, which enable light absorption and the production of heat due to their localized plasmon surface resonance [113]. Marketed as Temoporfin or Foscan over the past decade or so, the PS meso-tetrakis(3-hydroxyphenyl)chlorin is approved by the Food and Drug Administration (FDA) for PDT [114]. Therefore, a therapeutic modality that combines meso-tetrakis(3-hydroxyphenyl)chlorin-mediated PDT with gold NP-mediated PTT, based on a nanoconjugate made of NPs of gold and a capping shell of meso-tetrakis(3-hydroxyphenyl)chlorin, was reported to have a twofold synergistic enhancement of efficacy against the neuroblastoma-derived SH-SY5Y cells *in vitro* (**Figure 12**) [115]. In this study, the gold NPs were initially stabilized using mercaptopropionic acid, followed by esterification of the carboxylic acid functional groups of the mercaptopropionic acid with one of the phenolic groups of the PS, thus transforming the gold NP capping shell from carboxylic acid to a meso-tetrakis(3 hydroxyphenyl)chlorin shell. In addition to gold and graphene oxide, plasmonic NPs

**Figure 12.** *A nanoconjugate made of nanoparticles of gold with a capping shell of temoporfin.*

used in the combination of PDT with PTT include those of silver, silica, upconverting lanthanides, iron oxide, and several nanotubes [116].
